The Steric Hindrance of the Stepwise Reaction of N-Carboxy α-Amino Acid Anhydride with the α-Amino Acid Ester

Abstract

Abstract The mechanisms of the reactions of 4-alkyloxazolidinediones (1) (N-carboxy α-amino acid anhydrides(NCAs)) with α-amino acid benzyl ester p-toluenesulfonates (2) were investigated in acetonitrile containing triethylamine at low and room temperatures. Two types of reactions were observed: (1) the polymerization of NCAs was initiated with a small amount of 2 to produce polypeptides (6), and (2) the dipeptide benzyl esters (4) were produced by the stepwise reaction of NCAs with the esters. Both the polymerization and the dipeptide formation (1+2) seemed to be initiated by the nucleophilic attack of the amino group of the ester on the C-5 carbon of NCAs. The polymerization proceeded when the side chains of the amino acid esters (R2) were more bulky than those of the NCAs (R1). On the contrary, dipeptide esters were produced when the side chains of the NCAs (R1) were more bulky than those of the esters (R2).